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Research article:

Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study

Reference:

Evangelos Kontopantelis, David A Springate, David Reeves, Darren M Ashcroft, Martin Rutter, Iain Buchan, Tim Doran(2015) Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study. Diabetologia, doi: 10.1007/s00125-014-3473-8

Link to fulltext article
Abstract
Background: Observational data have been used to inform target levels for modifiable risk factors in type 2 diabetes but these data are limited by confounding. We aimed to describe the shape of observed relationships between risk factor levels and clinically important outcomes in type 2 diabetes after adjusting for multiple confounders. Methods: We used retrospective longitudinal data on 246,544 adults with type 2 diabetes from 600 practices contributing to the Clinical Practice Research Datalink between 2006 and 2012. Proportional hazards regression models quantified the risks of mortality, microvascular or macrovascular events associated with four modifiable risk factors: glycated haemoglobin (HbA1c), systolic and diastolic blood pressure and total cholesterol, while controlling for numerous patient and practice covariates. Findings: U-shaped relationships were observed between all-cause mortality and levels of the four risk factors. The lowest risks were associated with HbA1c 7.25-7.75%; total cholesterol 3.5-4.5 mmol/L; systolic blood pressure 135-145 mmHg; and diastolic blood pressure 82.5-87.5 mmHg. coronary and stroke mortality related to the four risk factors in a positive, curvilinear way, with the exception of blood pressure which related to coronary deaths in a U-shape. Macrovascular events showed a positive and curvilinear relationship with HbA1c but U-shaped for total cholesterol and systolic blood pressure. Microvascular related to the four risk factors in a curvilinear way: positive for HbA1c and systolic blood pressure but negative for cholesterol and diastolic blood pressure. Interpretation: We identified several relationships which, when considered in the light of relevant trial data, support a call for major changes to clinical practice. Most importantly, our results support trial data indicating that normalisation of glucose and blood pressure can lead to poorer outcomes, which makes a strong case for target ranges for these risk factors rather than target levels.
Author for correspondence
Evangelos Kontopantelis
Email for correspondence
E.Kontopantelis@manchester.ac.uk

Code list: res9: metformin

43 codes in list

Code Coding system Description Entity type List name multilexcode bnfcode bnfchapter
11990 CPRD_product_code metformin oral solution 500mg/5ml drug res9: metformin 14325001 06010202 Biguanides
16044 CPRD_product_code GLUCOPHAGE SR tablets 500mg [MERCK SER] drug res9: metformin 12946001 06010202 Biguanides
18220 CPRD_product_code pioglitazone with metformin tablets 15mg + 850mg drug res9: metformin 14374001 06010202/06010203 Biguanides/Other antidiabetic drugs
23 CPRD_product_code metformin tablets 500mg drug res9: metformin 2912001 06010202 Biguanides
25678 CPRD_product_code GLUCAMET tablets 500mg [OPUS] drug res9: metformin 8778001 06010202 Biguanides
26258 CPRD_product_code GLUCAMET tablets 850mg [OPUS] drug res9: metformin 8778002 06010202 Biguanides
27501 CPRD_product_code ORABET tablets 500mg [LAGAP] drug res9: metformin 4119001 06010202 Biguanides
30316 CPRD_product_code metformin with pioglitazone tablets 850mg + 15mg drug res9: metformin 14375001 06010202/06010203 Biguanides/Other antidiabetic drugs
31077 CPRD_product_code COMPETACT film coated tablets [TAKEDA] drug res9: metformin 14377001 06010202/06010203 Biguanides/Other antidiabetic drugs
31146 CPRD_product_code METSOL oral solution 500mg/5ml [ORBIS] drug res9: metformin 14326001 06010202 Biguanides
33087 CPRD_product_code METFORMIN tablets 500mg [ACTAVIS] drug res9: metformin 485009 06010202 Biguanides
33674 CPRD_product_code METFORMIN tablets 850mg [HILLCROSS] drug res9: metformin 486010 06010202 Biguanides
34004 CPRD_product_code METFORMIN tablets 500mg [IVAX] drug res9: metformin 1506010 06010202 Biguanides
34020 CPRD_product_code METFORMIN tablets 850mg [IVAX] drug res9: metformin 1506009 06010202 Biguanides
34135 CPRD_product_code METFORMIN tablets 500mg [M&A PHARM] drug res9: metformin 3888009 06010202 Biguanides
34323 CPRD_product_code METFORMIN tablets 500mg [HILLCROSS] drug res9: metformin 486009 06010202 Biguanides
34504 CPRD_product_code METFORMIN tablets 500mg [WOCKHARDT] drug res9: metformin 1345010 06010202 Biguanides
34598 CPRD_product_code METFORMIN tablets 500mg [GEN (UK)] drug res9: metformin 3149009 06010202 Biguanides
34697 CPRD_product_code METFORMIN tablets 850mg [WOCKHARDT] drug res9: metformin 1345009 06010202 Biguanides
34742 CPRD_product_code METFORMIN tablets 850mg [TEVA] drug res9: metformin 1874010 06010202 Biguanides
34836 CPRD_product_code METFORMIN tablets 850mg [ACTAVIS] drug res9: metformin 485010 06010202 Biguanides
34917 CPRD_product_code METFORMIN tablets 500mg [TEVA] drug res9: metformin 1874009 06010202 Biguanides
37874 CPRD_product_code vildagliptin with metformin tablets 50mg + 850mg drug res9: metformin 15988001 06010202/06010203 Biguanides/Other antidiabetic drugs
37902 CPRD_product_code vildagliptin with metformin tablets 50mg + 1000mg drug res9: metformin 15989001 06010202/06010203 Biguanides/Other antidiabetic drugs
38355 CPRD_product_code metformin modified release tablet 750mg drug res9: metformin 16266001 06010202 Biguanides
38400 CPRD_product_code GLUCOPHAGE SR tablets 750mg [MERCK SER] drug res9: metformin 16267001 06010202 Biguanides
38551 CPRD_product_code EUCREAS tablets 50mg + 1000mg [NOVARTIS] drug res9: metformin 15991001 06010202/06010203 Biguanides/Other antidiabetic drugs
39203 CPRD_product_code EUCREAS tablets 50mg + 850mg [NOVARTIS] drug res9: metformin 15990001 06010202/06010203 Biguanides/Other antidiabetic drugs
39560 CPRD_product_code BOLAMYN SR tablets 500mg [TEVA] drug res9: metformin 16380001 06010202 Biguanides
39598 CPRD_product_code metformin modified release tablet 1000mg drug res9: metformin 16967001 06010202 Biguanides
39729 CPRD_product_code GLUCOPHAGE SR tablets 1000mg [MERCK SER] drug res9: metformin 16968001 06010202 Biguanides
42161 CPRD_product_code ORABET tablets 500mg [SANDOZ] drug res9: metformin 12116001 06010202 Biguanides
43270 CPRD_product_code METFORMIN sugar free oral solution 500mg/5ml [ROSEMONT] drug res9: metformin 7016009 06010202 Biguanides
43619 CPRD_product_code sitagliptin with metformin tablets 50mg + 1000mg drug res9: metformin 16598001 06010202/06010203 Biguanides/Other antidiabetic drugs
43684 CPRD_product_code JANUMET tablets 50mg + 1000mg [M S D] drug res9: metformin 17931001 06010202/06010203 Biguanides/Other antidiabetic drugs
44250 CPRD_product_code METFORMIN oral solution 500mg/5ml [HILLCROSS] drug res9: metformin 6832009 06010202 Biguanides
45581 CPRD_product_code METABET SR tablets 500mg [MORNINGSID] drug res9: metformin 18298001 06010202 Biguanides
46989 CPRD_product_code METABET SR tablets 1000mg [MORNINGSID] drug res9: metformin 18655001 06010202 Biguanides
7048 CPRD_product_code metformin modified release tablet 500mg drug res9: metformin 12945001 06010202 Biguanides
7166 CPRD_product_code GLUCOPHAGE tablets 500mg [MERCK SER] drug res9: metformin 409001 06010202 Biguanides
735 CPRD_product_code metformin oral suspension 100mg/ml drug res9: metformin 12463001 06010202 Biguanides
7610 CPRD_product_code GLUCOPHAGE tablets 850mg [MERCK SER] drug res9: metformin 409002 06010202 Biguanides
93 CPRD_product_code metformin tablets 850mg drug res9: metformin 2912002 06010202 Biguanides

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